Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus

TLDR

Circadian oscillators are present in the SCN and peripheral tissues, with the SCN thought to entrain peripheral clocks through chemical signals. Sudden large changes in feeding time reset the phase of rhythmic gene expression gradually, likely via a clock‑dependent mechanism. Temporal feeding restriction can shift peripheral circadian gene expression by up to 12 h without affecting the SCN, indicating that metabolic changes can uncouple peripheral oscillators from the central pacemaker; the effect is faster in liver than in other tissues but converges after a week.

Abstract

In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light–dark or dark–dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.